Human corneal dystrophies and degenerations, which have been clinically documented are studied as keratoplasty specimens with histochemical stains, scanning and transmission electron microscopy, and immunologic techniques in an attempt to elucidate pathogenetic mechanisms. This approach has provided insight into cell-cell relationships in the normal and diseased states. Cell cultures performed in selected cases are examined by scanning and transmisson electron microscopy. Tissue and cell culture studies have demonstrated in vivo proliferation of corneal cells including epithelialization of the endothelial layer in corneas of three patients with posterior polymorphous dystrophy. In patients with macular corneal dystrophy intracellular and extracellular accumulation of fibrillogranular material was observed in the corneal stroma, Descemet's membrane and corneal endothelium. The presence and production of collagen, glycoconjugates, and collagenase has been investigated with immunofluorescent, electrophoretic, and chromatographic methods. Electron microscopic studies were performed on keratoconus and pellucid degeneration.